The present invention relates to methods and apparatus for delivering effective dosages of radiation therapy to selected sites in the body to inhibit proliferation of tissue, and particularly to selective localized enhancement of radiation dosage using low level sources.
As the average age of the population of the industrialized countries increases, and with it, the prolongation of exposure to environmental hazards, a corresponding increase is seen in the risk of cancer, and in the number of people with neoplasias and tumors. Radiation therapies which have heretofore been applied to treat tumors have had little differential effect. That is, to the extent that the dosage of radiation is effective to destroy or at least alter the growth rate of the tumor, it is also effective to place considerable stress and injury upon surrounding healthy or non-diseased tissue.
Interventional cardiology and interventional angiology have enjoyed increasing popularity in recent years for treating various vascular and duct disorders involving lesions. The numbers of implantations of prostheses for such treatment, and new applications that are under consideration, are growing rapidly with time, but new problems have arisen as well. For example, in treating carotid artery stenosis by a minimally invasive interventional procedure which removes or reduces the thickness of plaque on the inner lining of the vessel, the initial success of opening the lumen is often followed within only weeks by restenosis which is attributable to a neointimal hyperplasia reaction to the original procedure. This occurs in a significant percentage of the population of patients subjected to such a procedure, which appears to range from 20% to 35%, depending on the lesion type and length, the vessel size, and underlying basic conditions of the patient, such as diabetes mellitus.
Among solutions that have been proposed to inhibit, alleviate or prevent restenosis are the use of a radioactive stent which would serve to lessen or eliminate the healing response of hyperplasia, and/or coating of the stent with a biodegradable carrier which would disintegrate over time when the stent is deployed in a blood vessel, to release anti-proliferative substances incorporated therein. These procedures, however, would necessarily be used for all angioplasty patients because it cannot presently be determined which patients will be among the approximately 20% to 35% who will suffer restenosis as a result of proliferation of tissue in the healing response. Thus, about 65% to 80% of angioplasty patients who receive a radioactive stent, for example, would not have actually developed a restenosis, and would not have had to be subjected to treatment for an adverse reaction to the procedure.
It is a principal aim of the present invention to provide a method and means of treating angioplasty patients and other patients who are subjected to tissue trauma in a body vessel, duct, tract or other passageway in the body sought to be relieved from an obstruction, that actually leads to an acute restenosis, without need to perform a subsequent or even concurrent prophylactic and possibly injurious treatment on every patient who receives an angioplasty or related procedure, a large percentage of which will not experience the restenosis.
Additionally, it has been found that especially with the increasing number of prosthetic implants being performed in surgery, orthopedics and dental medicine, a certain percentage of the patients will suffer from an enhanced foreign body reaction. For example, when a hip prosthesis is implanted the patient may experience a reaction of the surrounding tissue which can compromise the healing process and the firmness or retention of the implant. This same problem is encountered in a measurable percentage of patients who receive dental and other surgical implants.
Accordingly, a related aim of the invention is to provide a localized form of treatment that allows such foreign body reaction to be selectively addressed in only those patients who suffer the problem, and to deliver the treatment in a way that is effective without any significant potential for harm to adjoining or nearby tissue that may be exposed to the treatment.
In efforts to treat localized solid tumors in the body, with an ever-increasing number of procedures owing to an increasing rate of tumors in the bronchial system and in the abdominal intestines, surgical removal may not be a viable option especially if the malignancy has metastasized and spread to other portions of the body. In many instances, the tumor may cause blockage of a duct or passage. A stent may be implanted to keep the lumen open, such as in the lumen of a bronchial passage or of a duct in the gall bladder, but experience has shown that tumor growth can again cause the lumen to become occluded. A localized action to slow or inhibit tumor growth would be desirable to prevent or reduce such occlusion.
It is known that the capacity to inhibit solid tumor growth and even destroy the tumor, by means of ionizing radiation treatment, depends on the types of cells involved and their sensitivity to radiation. Each individual tissue has its own sensitivity to radiation. Exposure of the skin to mild radiation can produce a skin burn, whereas exposure to larger doses can produce a skin necrosis. In the case of treatment of a tumor in the body, it is desirable to use a higher level of radiation, sufficient to produce a radiation dose at or near the tumor site in a range upward of 20 Gray (Gy). Delivery of a dosage in the range from about 20 to 200 Gy to the tumor site can be effective to induce necroses or apoptosis in the tumor and inhibit further growth, but typically the externally generated radiation (usually a beam of X-rays or accelerated electrons using a collimator, rather than a mass of radioactive material as had been the technique in the earliest treatment) is directed toward a tumor deep below the skin. Only rarely is the tumor at or directly beneath the skin, the much more frequent situation being that considerable healthy tissue lies between the skin and the tumor site. To deliver a dose of radiation adequate to have a desired effect on the tumor (albeit that it may not be completely successful, even over several sessions of the radiation treatment) it is necessary to accept the likelihood that intervening healthy tissue may be severely harmed by the impinging radiation. For example, in the case of liver carcinoma or a metastasis in the liver that requires treatment, it is necessary to penetrate not only the skin, fatty tissue and bowel that overlie the site of the metastasis with the radiation, but also the normal and still functional liver tissue in its path.
It is therefore another important aim of the present invention to provide a method and means for locally enhancing the therapeutic effects of radiation treatment of relatively deep body tumors, in a way that will allow effective treatment of the tumor with considerably lower doses of radiation than would otherwise be required, so that non-diseased tissue is subjected to substantially less harmful effect.
Still another important objective of the invention is to utilize locally enhanced radiation therapy to make a tumor more susceptible to attack and eradication by other forms of tumor treatment, such as cytostatic therapy, chemotherapy, genetically engineered drug therapy, or cancer gene therapy. In the latter treatment as proposed, genes which have been altered to render them damaged or defective as a possible result of cigarette smoking, excessive exposure to sunlight or toxic chemicals, for example, are repaired or replaced by inserting other genes carried by modified viruses into the cancer cells.